chr13-49467916-C-T

Variant names:

• chr13-49467916-C-T
• rs77248806
• NM_001160308.3:c.261C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001160308.3(SETDB2):​c.261C>T​(p.Pro87Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,610,756 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (7 hom.)
• Consequence: SETDB2 NM_001160308.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12
• Publications: 0 publications found

Genes affected

SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

SETDB2-PHF11 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 13-49467916-C-T is Benign according to our data. Variant chr13-49467916-C-T is described in ClinVar as Benign. ClinVar VariationId is 768617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00534 (812/152182) while in subpopulation AFR AF = 0.0181 (753/41528). AF 95% confidence interval is 0.0171. There are 7 homozygotes in GnomAd4. There are 367 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160308.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB2	NM_001160308.3	MANE Select	c.261C>T	p.Pro87Pro	synonymous	Exon 5 of 14	NP_001153780.1	Q96T68-2
	SETDB2-PHF11	NM_001320727.2		c.261C>T	p.Pro87Pro	synonymous	Exon 5 of 20	NP_001307656.1
	SETDB2	NM_031915.3		c.297C>T	p.Pro99Pro	synonymous	Exon 6 of 15	NP_114121.2	Q96T68-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB2	ENST00000611815.2	TSL:5 MANE Select	c.261C>T	p.Pro87Pro	synonymous	Exon 5 of 14	ENSP00000482240.2	Q96T68-2
	SETDB2	ENST00000354234.8	TSL:1	c.297C>T	p.Pro99Pro	synonymous	Exon 6 of 15	ENSP00000346175.5	Q96T68-1
	SETDB2	ENST00000317257.12	TSL:1	c.261C>T	p.Pro87Pro	synonymous	Exon 4 of 13	ENSP00000326477.9	Q96T68-2

Frequencies

GnomAD3 genomes AF: 0.00535 AC: 813 AN: 152064 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00145 AC: 361 AN: 248856 AF XY: 0.00107

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000996

GnomAD4 exome AF: 0.000618 AC: 902 AN: 1458574 Hom.: 7 Cov.: 30 AF XY: 0.000565 AC XY: 410 AN XY: 725652

African (AFR) AF: 0.0198 AC: 660 AN: 33328

American (AMR) AF: 0.00142 AC: 63 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39428

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52710

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5758

European-Non Finnish (NFE) AF: 0.0000756 AC: 84 AN: 1110850

Other (OTH) AF: 0.00131 AC: 79 AN: 60236

GnomAD4 genome AF: 0.00534 AC: 812 AN: 152182 Hom.: 7 Cov.: 32 AF XY: 0.00493 AC XY: 367 AN XY: 74390

African (AFR) AF: 0.0181 AC: 753 AN: 41528

American (AMR) AF: 0.00314 AC: 48 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67988

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00231 Hom.: 1

Bravo AF: 0.00618

Asia WGS AF: 0.00116 AC: 4 AN: 3474

EpiCase AF: 0.000219

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.0
DANN	Benign	0.41
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77248806; hg19: chr13-50042052;